Silver as a Cure for Ebola - Literature Collection

IMSL

INDUSTRIAL MICROBIOLOGICAL SERVICES LTD

Technical White Paper: Antimicrobial Activity of Silver V1.0 - September 2005

The antimicrobial activity of silver has been recognised by clinicians for over 100 years (Ref 1). In
addition, reports suggest that hygienic benefits have been associated with the use of silver for considerably
longer. Records show that Hippocrates recognised the role of silver in the prevention of disease and
accounts exist that suggest that the romans stored wine in silver vessels to prevent spoilage (Ref 2).
However, it is only in the last few decades that the mode of action of silver as an antimicrobial agent has
been studied with any rigour (eg Ref 3).

Metallic silver is relatively unreactive however, when exposed to aqueous environments some ionic silver
(Ag + ) is released. Certain salts (eg silver nitrate) are readily soluble in water and have been exploited
as antiseptic agents for many decades (Ref. 1). The generation of silver ions can also be achieved
through ion exchange using complexes of silver with other inorganic materials (eg silver - zeolite
complexes; Ref. 4). Silver nano-particles have also been demonstrated to exhibit antimicrobial properties
both against bacteria (Ref 5) and viruses (Ref 6) with close attachment of the nano-particles themselves
with the microbial cells / virus particles being demonstrated with activity being size dependent (Ref 7).
Despite this, the principle activity of silver is as a results of the production of silver ions within an aqueous
matrix (Ref 8). This therefore implies that for silver to have an antimicrobial effect, free water must be
present.

Silver ions interact with a number of components of both bacterial, protozoal and fungal cells. Toxicity
to microbial cells is exhibited at very low concentrations with masses within the range of a few fg cell 1
being associated with bactericidal activity (Ref 9). The kinetics of kill vary depending on the source of
silver ions with silver derived from ion exchange processes demonstrating delayed activity compared with
that derived from soluble salts (Ref 9). Activity appears to increase with temperature and pH (Ref 9).
Studies have demonstrated that silver ions interact with sulfydryl (-SH) groups of proteins as well as the
bases of DNA leading either to the inhibition of respiratory processes (Ref 10) or DNA unwinding
(Ref 11). Inhibition of cell division and damage to bacterial cell envelopes is also recorded (Ref 12) and
interaction with hydrogen bonding processes has been demonstrated to occur (Ref 13). Interruption of
cell wall synthesis resulting in loss of essential nutrients has been shown to occur in yeasts (Ref 14) and
may well occur in other fungi. Antiviral activity of silver ions has been recorded and interaction with -SH
groups has been implicated in the mode of action (Ref 15). The association of silver nano-particles with
the envelope of certain viruses has been suggested to prevent them from being infective (Ref 6). Much
of the research into the mechanism of action of silver ions has been associated with its use as a
therapeutic agent especially as a topical dressing on burns. The concentration employed in and released
from treated articles is significantly lower than in these applications (Ref 9). Under such conditions it has
been suggested that in many cases the concentration of silver ions available following hydration of the
surface of a treated article is too low to produce antimicrobial activity associated with many of the
mechanisms described above. However, silver ions have been demonstrated to interact with the proteins
and possibly phospholipids associated with the proton pump of bacterial membranes. This results in a
collapse of the membrane proton gradient causing a disruption of many of the mechanisms of cellular
metabolism and hence cell death (Ref 16).

Silver ions clearly do not possess a single mode of action. They interact with a wide range of molecular
processes within microorganisms resulting in a range of effects from inhibition of growth, loss of
infectivity to cell death. The mechanism depends on both the concentration of silver ions present and the
sensitivity of the microbial species to silver. Contact time, temperature, pH and the presence of free
water all impact on both the rate and extent of antimicrobial activity. However, the spectrum of activity
is very wide and the development of resistance relatively low, especially in clinical situations (Ref 17).

Industrial M icrobiological Services Ltd Registered in England N o 3264423 Registered Office The 0 ddf el lows H all Oxford Road Reading BerkshireRGl 7N G

References

1 Lansdown A B G (2002), Silver I: Its Antibacterial Properties and Mechanism of Action, J
Wound Care 11, 5, 173.

2 Sturgis S (2005), Precious Metal - Foot Care Takes a Shine to Silver, Biomechanics February
2005.

3 Brown, M R W, Anderson R A (1968), The Bactericidal Effect of Silver Ions on Pseudmonas
aeruginosa, J Pharm Pharacol. 20 (Supplement), 1 - 3.

4 Im K, Takasaki Y, Endo A, Kuriyama M (1996), Antibacterial Activity of A-Type Zeolite
Supporting Silver Ions in Distilled Water. J Antibacterial Antifungal Agents, 24, 269 - 274.

5 Sondi I, Salopek-Sondi B (2004), Silver Nanoparticles as Antimicrobial Agent: A Case Study on
E coli as a Model for Gram-Negative Bacteria, J Colloid Interface Sci 275, 177 - 182.

6 Elchiguerra JLetal (2005), Interaction of Silver Nanoparticles with HIV-I, J Nanobiotechnology
3, 6.

7 Morones J R et al (2005) The Bactericidal Effect of Silver Nanoparticles, Nanotechnology 16,
2346 -2353.

8 McDonnell G, Denver R (1999), Antiseptics and Disinfectants: Activity, Action and Resistance,
Clinical Microbiol Reviews, 12, 1, 147 - 179.

9 Matsumura Y, Yoshikata K, Kunisaki S-I, Tsuschido T (2003), Mode of Bactericidal Action of
Silver Zeolite and Its Comparison with that of Silver Nitrate, App Env Micro 69, 7, 4278 - 4281.

10 Bragg P D, Rannie D J (1974), The Effect of Silver Ions on the Respiratory Chain of E coli Can
J Microbiol, 20, 883 - 889.

11 Batarseh K I (2004), Anomaly and Correlation of Killing in the Therapeutic Properties of Silver
(I) Chelation with Glutamic and Tartaric Acids, JAntimicrobial Chemotherapy 54, 546-548

12 Richards R M E, Taylor R B, Xing D K L (1984), Effect of Silver on Whole Cells and
Speroplasts of a Silver Resistant Pseudomonas aeruginosa, Microbios 39, 151 - 158.

13 Russell A D , Hugo W B (1994), Antimicrobial Activity and Action of Silver, Prog. Med. Chem,
31,351 - 371.

14 Wells TN,etal(l 995), Mechanism of Irreversible Inactivation of Phosphomannose Isomerases
by Silver Ions and Flamazine, Biochemistry 34, 24, 896 - 903.

15 Thurmann R B, Gerba C P (1989), The Molecular Mechanisms of Copper and Silver Ion
Disinfection of Bacteria and Viruses, Crit Rev Environ Control, 18, 295 - 315.

16 Dibrov P, et al (2002), Chemiosmotic Mechanism of Antimicrobial Activity of Ag + in Vibrio
cholerae, Antimicrobial Agents and Chemotherapy, 46, 8, 2668 - 2670.

17 Cooper R (2004), A Review of the Evidence for the use of Topical Antimicrobial Agents in
Wound Care, World Wide Wounds, February 2004.

Industrial M icrobiological Services Ltd Registered in England N o 3264423 Registered Office The 0 ddf el lows H all Oxford Road Reading BerkshireRGl 7N G